PROJECT SUMMARY This multi-PI (MPI) proposal is aligned with the mission of the NIAMS Clinical Observation Studies R01 FOA to enhance the quality of clinical trials in cutaneous lupus erythematosus (CLE). The objectives of this proposal are to characterize disease activity courses of patients with CLE and benchmark outcome measures that adequately demonstrate treatment efficacy. Dr. Benjamin Chong (MPI) at University of Texas Southwestern Medical Center and Dr. Victoria Werth (MPI) at University of Pennsylvania are well positioned to carry out this observational study of patients with CLE. We have collected longitudinal clinical and quality of life data from over 700 patients with CLE that produced important findings about the disease course of CLE patients. However, our data's applicability for clinical trial design is restricted by lack of standardized time points. Thus, we propose a rigorous 24-week observational study with four visits spaced eight weeks apart to address these limitations. Our first aim seeks to define disease activity courses over a 24-week period in patients with CLE. We will follow the patients' Cutaneous Lupus Erythematosus Activity and Severity Index (CLASI) activity scores over time. We also will compare frequencies of and characteristics of patients with improving, stable, and worsening disease activities. We hypothesize that patients on standard-of-care treatments for CLE will mostly demonstrate improvement in disease activity, thus making the data suitable for clinical trials to compare. Our second aim is to establish a benchmark for the amount of improvement in CLASI activity score that is sufficient for treatment efficacy. We propose comparing percentage changes of CLASI activity scores with physician and patient assessments of change in disease activity between weeks 0 and 24. We hypothesize that attaining at least 50% improvement in CLASI activity scores can be used as a benchmarked endpoint to demonstrate treatment efficacy. Our third aim will focus on changes in patient- reported outcome measure scores in patients with CLE as endpoints for therapeutic efficacy. We will compare changes in scores of patient-reported outcome measures such as the SKINDEX-29+3 questionnaire at weeks 0 and 24. We will also compare score changes in patients stratified by their percentage change in CLASI activity scores. We hypothesize that a decrease of at least 10 in SKINDEX-29+3 scores can be a benchmarked patient-reported outcome measure. Thus, clinical trials with CLE patients may use these data as guidelines to determine whether patients experience therapeutic benefit. This proposal will provide future clinical trials in CLE with the following deliverables: 1) natural disease control data to be used for comparison, 2) standardized outcome measures for therapeutic efficacy, which set benchmarks of improvement in CLASI activity scores and patient-reported outcome measure scores such as the SKINDEX-29+3. With this knowledge, clinical trials will be able to distinguish promising therapeutics in CLE.